Inflammation in sepsis is associated with hypercoagulation that may lead to thrombosis and disseminated intravascular coagulation. Conventional diagnostic assays are poorly sensitive to procoagulant changes in sepsis. Objectives of the article is to study changes in hemostatic state of septic patients using spatial clot growth assay (currently being developed under the trademark of thrombodynamics) and to compare the sensitivity of this method with the sensitivity of conventional methods. Sixteen patients with hematological malignancies and sepsis were enrolled in the study. All patients had been surveyed for a month following the infection onset. Spatial clot growth assay monitors fibrin clot development in a nonstirred thin layer of platelet-free plasma activated by immobilized tissue factor. Clotting time tests, thromboelastography, D-dimer assays were also performed. Spatial clot growth revealed hypercoagulation in six patients. D-dimer levels increase (with vein thrombosis in one case) was subsequently observed in five of them. D-dimer levels did not increase when spatial clot growth was normal. At the next time point, after spatial clot growth assay showed hypercoagulation, the mean D-dimer concentration was significantly higher than after a normal analysis (457 versus 234 μg/l; P < 0.05); there was no such correlation for other assays. The remaining 10 patients had elevated D-dimer levels on the first day; this either decreased gradually or remained elevated. Spatial clot growth showed normalization in survivors and growing hypocoagulation in nonsurvivors. Measuring spatial clot growth dynamics has potential diagnostic utility for the evaluation of thrombotic risk.

Patients with multiple myeloma (MM) are at increased risk of venous thromboembolism. Therefore, adequate laboratory control of hemostasis and subsequent adjustments of anticoagulant therapy are necessary. We studied hemostasis changes using thromboelastography (TEG), thrombin generation test (TGT) and thrombodynamics (TD) in primary MM patients (PMMpt, n = 25) and patients in remission (RMMpt, n = 34) during blood stem cell (BSC) mobilization. TD and TEG reveal hypercoagulability in PMMpt (*p < 0.05) in relation to healthy volunteers. There was no difference in any of the tests between PMMpt and RMMpt. We detected no heparin effect in 22% of patients one day after the onset of the prophylactic heparin treatment (500 IU/h) during BSC mobilization; tests shifted toward the hypercoagulability in 75% of patients one day after cyclophosphamide (4 g/m²) chemotherapy. Global hemostasis tests were in good agreement with each other, revealed hypercoagulability and heparin “resistance” in patients with MM and may be useful for therapy individualization.

Summary. Background: Tissue factor pathway inhibitor (TFPI) is a major regulator of clotting initiation and a promising target for pro‐ and anticoagulation therapy. The aptamer BAX499 (formerly ARC19499) is a high‐affinity specific TFPI antagonist designed to improve hemostasis. However, it is not clear how stimulation of coagulation onset by inactivating TFPI will affect spatial and temporal clot propagation. Objective: To examine the BAX499 effect on clotting in a spatial, reaction‐diffusion experimental system in comparison with that of recombinant activated factor VII (rVIIa). Methods: Clotting in plasma activated by immobilized tissue factor (TF) was monitored by videomicroscopy. Results: BAX499 dose‐dependently improved coagulation in normal and hemophilia A plasma activated with TF at 2 pmole m⁻² by shortening lag time and increasing clot size by up to ∼2‐fold. The effect was TFPI specific as confirmed by experiments in TFPI‐depleted plasma with or without TFPI supplementation. Clotting improvement was half‐maximal at 0.7 nm of BAX499 and reached a plateau at 10 nm, remaining there at concentrations up to 1000 nm. The BAX499 effect decreased with TF surface density increase. RVIIa improved clotting in hemophilia A plasma activated with TF at 2 or 20 pmole m⁻², both by shortening lag time and increasing spatial velocity of clot propagation; its effects were strongly concentration dependent. Conclusions: BAX499 significantly improves spatial coagulation by inhibiting TFPI in a spatially localized manner that is different to that observed with rVIIa.

Heparin therapy and prophylaxis may be accompanied by bleeding and thrombotic complications due to individual responses to treatment. Dosage control based on standard laboratory assays poorly reflects the effect of the therapy. The aim of our work was to compare the heparin sensitivity of new thrombodynamics (TD) assay with sensitivity of other standard and global coagulation tests available to date. A total of 296 patients with high risk of venous thromboembolism (deep vein thrombosis (DVT), early postoperative period, hemoblastosis) were enrolled in the study. We used a case-crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to the hemostatic state before and after unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the activated partial thromboplastin time (APTT), anti-Xa activity test, thrombin generation test (TGT) and thromboelastography (TEG). A receiver operating characteristic (ROC) curve analysis was used to evaluate changes before and after heparin prophylaxis and therapy. Blood was sampled before heparin injection, at the time of maximal blood heparin concentration and before the next injection. Hypercoagulation before the start of heparin treatment was detected by TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal for TD and anti-Xa, intermediate for TGT and TEG and minimal for APTT. These results indicate that TD has a high sensitivity to the effects of UFH and LMWH after both prophylactic and therapeutic regimes and may be used for heparin monitoring.